6533b7ddfe1ef96bd1273619
RESEARCH PRODUCT
Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases
Stylianos E. AntonarakisRafael PulidoCaroline TapparelAnabel GilJosema TorresMiguel ValienteBeatriz GomarAmparo Andrés-ponssubject
Tumor Suppressor Proteins/chemistry/ metabolismTime FactorsAmino Acid MotifsPlasma protein bindingBiochemistryMicrotubulesSerineDiscs Large Homolog 1 ProteinProtein structureSaccharomyces cerevisiae/metabolismPhosphorylationGlutathione Transferaseddc:616Nucleoside-Phosphate Kinase/metabolismbiologyChemistryDystrophin-Associated Proteins/ chemistrySignal transducing adaptor proteinProtein-Serine-Threonine Kinases/metabolismRecombinant Fusion Proteins/chemistryGuanylate KinaseCell biologyCOS CellsMicrotubule-Associated Proteins/metabolismPhosphorylationProteins/metabolismGlutathione Transferase/metabolismMicrotubule-Associated ProteinsMicrotubules/ metabolismPlasmidsProtein BindingCèl·lulesRecombinant Fusion ProteinsPDZ domainSaccharomyces cerevisiaeProtein Serine-Threonine KinasesTransfectionModels BiologicalTwo-Hybrid System TechniquesDiscs Large Homolog 1 ProteinPTENAnimalsHumansImmunoprecipitationProteïnes supressores de tumorsMolecular BiologyAdaptor Proteins Signal TransducingTumor Suppressor ProteinsPTEN PhosphohydrolaseProteinsMembrane ProteinsCell BiologyPlasmids/metabolismPhosphoric Monoester HydrolasesProtein Structure TertiaryDystrophin-Associated ProteinsMutationCancer researchbiology.proteinNucleoside-Phosphate KinaseCarrier ProteinsGuanylate KinasesPhosphoric Monoester Hydrolases/chemistry/ metabolismdescription
The tumor suppressor phosphatase PTEN is a key regulator of cell growth and apoptosis that interacts with PDZ domains from regulatory proteins, including MAGI-1/2/3, hDlg, and MAST205. Here we identified novel PTEN-binding PDZ domains within the MAST205-related proteins, syntrophin-associated serine/threonine kinase and MAST3, characterized the regions of PTEN involved in its interaction with distinctive PDZ domains, and analyzed the functional consequences on PTEN of PDZ domain binding. Using a panel of PTEN mutations, as well as PTEN chimeras containing distinct domains of the related protein TPTE, we found that the PTP and C2 domains of PTEN do not affect PDZ domain binding and that the C-terminal tail of PTEN (residues 350-403) provides selectivity to recognize specific PDZ domains from MAGI-2, hDlg, and MAST205. Binding of PTEN to the PDZ-2 domain from MAGI-2 increased PTEN protein stability. Furthermore, binding of PTEN to the PDZ domains from microtubule-associated serine/threonine kinases facilitated PTEN phosphorylation at its C terminus by these kinases. Our results suggest an important role for the C-terminal region of PTEN in the selective association with scaffolding and/or regulatory molecules and provide evidence that PDZ domain binding stabilizes PTEN and targets this tumor suppressor for phosphorylation by microtubule-associated serine/threonine kinases.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-01-01 |